Dr. Fenske on the Utility of Next-Generation BTK Inhibitors in MCL

Timothy Fenske, MD, MS, associate professor at the Medical College of Wisconsin, discusses the utility of next-generation BTK inhibitors in mantle cell lymphoma (MCL).

Quite a few next-generation inhibitors are in development, says Fenske. Two classes of BTK inhibitors exist in MCL: covalent inhibitors and noncovalent inhibitors. Acalabrutinib (Calquence) and ibrutinib (Imbruvica) covalently bind to the BTK enzyme and when there is a mutation where the drug resides, then it cannot bind anymore; this leads to the development of resistance,explains Fenske. A new category of BTK inhibitors are noncovalent binders that still appear to block the enzyme in vitro, even when that mutation is present.

The field can envision a day, hopefully not too far down the road, when a patient with MCL who shows resistance to ibrutinib or acalabrutinib could have a BTK mutation analysis performed and that would inform which BTK inhibitor they should be switched to, concludes Fenske.